The expanding scope and impact of epigenetic cytosine modifications.

The expanding scope and impact of epigenetic cytosine modifications.
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DOI:
10.1016/j.cbpa.2016.05.029
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发表时间:
2016-08
影响因子:
7.8
通讯作者:
Kohli RM
Kohli RM
中科院分区:
生物学2区
文献类型:
--
作者:
Liu MY;DeNizio JE;Schutsky EK;Kohli RM

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基因组DNA的化学修饰可以扩展和塑造其编码潜力。特别是胞嘧啶甲基化在调节基因表达和确定细胞身份方面具有良好的作用。TET家族酶的发现开辟了DNA甲基化之外的重要前沿,揭示了三种氧化形式的胞嘧啶可以介导DNA去甲基化或编码独立的表观遗传功能。化学生物学在揭示TET复杂的反应机制和令人惊讶的各种底物上的反应性范围方面发挥了重要作用。此外,创新的化学酶策略已经能够在体外和体内灵敏地检测氧化胞嘧啶产物。我们强调了最近的关键发展,展示了化学生物学如何推进我们对扩展的、动态的表观基因组的理解。
Chemical modifications to genomic DNA can expand and shape its coding potential. Cytosine methylation in particular has well-established roles in regulating gene expression and defining cellular identity. The discovery of TET family enzymes opened a major frontier beyond DNA methylation, revealing three oxidized forms of cytosine that could mediate DNA demethylation or encode independent epigenetic functions. Chemical biology has been instrumental in uncovering TET’s intricate reaction mechanisms and scope of reactivity on a surprising variety of substrates. Moreover, innovative chemoenzymatic strategies have enabled sensitive detection of oxidized cytosine products in vitro and in vivo. We highlight key recent developments that demonstrate how chemical biology is advancing our understanding of the extended, dynamic epigenome.
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